A common 'ancestral' C(-55) variant of the NPRC P1 promoter is associated with lower ANP levels and higher SBP and MBP in obese hypertensives. The C(-55) variant, in the presence of increased adiposity, might reduce plasma ANP through increased NPRC-mediated ANP clearance, contributing to higher blood pressure.

The expression of the natriuretic peptide clearance receptor is abundant in human and rat adipose tissue, where it is specifically inhibited by fasting. In obese hypertensives, plasma atrial natriuretic peptide (ANP) levels were found to be lower than in obese normotensives. Therefore, the increased adipose mass might influence ANP levels and/or its biological activity. The aim of the present study was to evaluate whether the humoral, hemodynamic, and renal effects of exogenous ANP in obese hypertensives might be enhanced by a very low calorie diet. Eight obese hypertensives received a bolus injection of ANP (0.6 mg/kg) after 2 weeks of a normal calorie/normal sodium diet, and blood pressure (BP), heart rate, ANP, cGMP, plasma renin activity, and aldosterone were evaluated for 2 hours before and after the injection. Diuresis and natriuresis were measured every 30 minutes. The patients then started a low calorie/normal sodium diet (510 kcal/150 mmol/d) for 4 days, and then the ANP injection protocol was repeated. The low calorie diet induced a slight weight loss (from 90.61.1 to 87.71.2 kg; P0.01), which was accompanied by increase of cGMP excretion (from 146.010.1 to 154.59.5 nmol/24 h; P0.05) together with a reduction of BP (P0.01 versus basal levels). ANP injection after diet was followed by an increase of ANP levels similar to that observed before diet, but plasma cGMP, diuresis, and natriuresis increased significantly only after diet. Similarly, the decrease of BP after ANP administration was significantly higher after diet (change in mean arterial pressure, 6.40.7 versus 4.00.6 mm Hg; P0.05) as well as that of aldosterone (P0.01). These data show that a low calorie diet enhances the humoral, renal, and hemodynamic effects of ANP in obese hypertensives and confirm the importance of caloric intake in modulating the biological activity of ANP, suggesting that the natriuretic peptide system can play a role in the acute changes of natriuresis and diuresis associated with caloric restriction. (Hypertension. 1999;33:658-662.) Key Words: obesity hypertension natriuretic peptides, atrial cyclic GMP diuresis natriuresis S everal epidemiological and clinical studies have shown that excess weight and weight gain contribute to increase blood pressure (BP) in a large proportion of hypertensive patients. 1-3 Such studies have also demonstrated that BP in the adult is highly correlated to body mass index (BMI). 4,5 Although the association between obesity and hypertension is widely recognized, the pathophysiology of weight-related change in BP is a matter of debate. Several mechanisms have been suggested to play a role in the pathogenesis of obesity-related hypertension, such as increased plasma volume and cardiac output, 6 enhanced sympathetic nervous system activity , 7 hyperinsulinemia and insulin resistance, 8 and nutritional factors such as high sodium intake and/or sodium retention. 9 Moreover, the importance of weight gain per se in causing hypertension is reinforced by experimental studies showing that weight gain ...

The angiotensinogen G(-6)A variants do not affect cardiovascular parameters in young adults, but an effect of this polymorphism on cardiovascular phenotype (and hypertension) in older adults cannot be excluded. Additional factors, associated with ageing, should be present to unleash the supposed unfavourable potential of the (-6)A angiotensinogen variant.

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